tbuckley/cabot-search huggingface dataset:
Long-term overall survival (os) and prognostic factors of patients (pts) with surgery of liver metastases from colorectal cancer origin (lm/crc): Retrospective analysis of a Spanish single institution
Authors: I. R. Quispe, F. J. Ramos, I. Bilbao, T. Macarulla, S. Cedres, R. Charco, J. Lázaro, M. Moreiras, M. Moreiras, J. Tabernero
Journal: Journal of Clinical Oncology (2009)

e15052 Background: Hepatectomy is the only potentially curative treatment for LM/CRC. Long-term survival following liver resection (LR) has improved. The aim of this study was to analyze prognostic factors and OS after LR Methods: A retrospective review of the medical records of pts who underwent LR for LM/CRC from 1997 to 2007 was conducted. Multiple potential prognostic factors for survival were analyzed: synchronic vs. metachronic, post-op chemotherapy (CT) vs. no, lymph node (LN) status of primary tumor, R 0 vs. R 1–2 resection, gender, location of primary tumor, number and size of metastases, and unilobar vs. bilobar disease. Results: 190 pts (colon 130, rectum 60) underwent LR. Pts’ characteristics: 123 male, 67 female; median age 63 yrs (32–85); 95 pts synchronic, 95 metachronic; 145 pts (76%) received post-op CT; LN status was p N 0 in 61 (32%) pts, p N 1 in 74 (39%) and p N 2 in 52 (27%). A R 0 resection was performed in 164 (86%) and R 1 in 25 (13%). Post-op mortality was 2.6%.Median OS was 68 months with 5- and 10-year OS of 52% and 31%, and 5- and 10-year disease free survival of 36% and 18%. 5-year OS differed between metachronic and synchronic (64% vs. 39%; p&lt;0.001); LN-status (73% for p N 0 vs. 41% for p N 1–2; p&lt;0.001); R 0 /R 1–2 surgery (58% for R 0 vs. 21% for R 1- 2 ; p=0.002). With a median follow-up of 70 months, 71 (37%) pts remained free of disease, 60 (32%) had new metachronic LM/CRC, 18 (9.5%) had LM/CRC and extrahepatic disease and 36 (19%) had extrahepatic disease alone. Non-significant factors for prognosis were gender, location of primary tumor, number and size of metastases, bilobar disease and adjuvant CT. Conclusions: Pts with LM/CRC who undergo liver resection can achieve long-term OS, our data identifying as prognostic factors: LN status, synchronic/metachronic disease and Type of resection (R 0 ). No significant financial relationships to disclose.
Pan-cancer proteomic map of 949 human cell lines
Authors: Emanuel Gonçalves, Rebecca C. Poulos, Zhaoxiang Cai, Syd Barthorpe, Srikanth S. Manda, Natasha Lucas, Alexandra Beck, Daniel Bucio-Noble, Michael Dausmann, Caitlin Hall, Michael Hecker, Jennifer Koh, Howard Lightfoot, Sadia Mahboob, Iman Mali, James Morris, Laura Richardson, Akila J. Seneviratne, Rebecca Shepherd, Erin Sykes, Frances Thomas, Sara Valentini, Steven G. Williams, Yangxiu Wu, Dylan Xavier, Karen L. MacKenzie, Peter G. Hains, Brett Tully, Phillip J. Robinson, Qing Zhong, Mathew J. Garnett, Roger R. Reddel
Journal: Cancer Cell (2022)

The proteome provides unique insights into disease biology beyond the genome and transcriptome. A lack of large proteomic datasets has restricted the identification of new cancer biomarkers. Here, proteomes of 949 cancer cell lines across 28 tissue types are analyzed by mass spectrometry. Deploying a workflow to quantify 8,498 proteins, these data capture evidence of cell-type and post-transcriptional modifications. Integrating multi-omics, drug response, and CRISPR-Cas9 gene essentiality screens with a deep learning-based pipeline reveals thousands of protein biomarkers of cancer vulnerabilities that are not significant at the transcript level. The power of the proteome to predict drug response is very similar to that of the transcriptome. Further, random downsampling to only 1,500 proteins has limited impact on predictive power, consistent with protein networks being highly connected and co-regulated. This pan-cancer proteomic map (ProCan-DepMapSanger) is a comprehensive resource available at https://cellmodelpassports.sanger.ac.uk.
Machine-Learning Score Using Stress CMR for Death Prediction in Patients With Suspected or Known CAD
Authors: Théo Pezel, Francesca Sanguineti, Philippe Garot, Thierry Unterseeh, Stéphane Champagne, Solenn Toupin, Stéphane Morisset, Thomas Hovasse, Alyssa Faradji, Tania Ah-Sing, Martin Nicol, Lounis Hamzi, Jean Guillaume Dillinger, Patrick Henry, Valérie Bousson, Jérôme Garot
Journal: JACC. Cardiovascular imaging (2022)
A Longitudinal Study on the Impact of Indoor Temperature on Heat-Related Symptoms in Older Adults Living in Non–Air-Conditioned Households
Authors: Anaïs Teyton, Mathieu Tremblay, Isabelle Tardif, Marc-André Lemieux, Kareen Nour, Tarik Benmarhnia
Journal: Environmental Health Perspectives (2022)

Background: Both chronic and acute heat result in a substantial health burden globally, causing particular concern for at-risk populations, such as older adults. Outdoor temperatures are often assessed as the exposure and are used for heat warning systems despite individuals spending most of their time indoors. Many studies use ecological designs, with death or hospitalizations rates. Individual-level outcomes that are directly related to heat-symptoms should also be considered to refine prevention efforts. Objectives: In this longitudinal study, we assessed the association between indoor temperature and proximal symptoms in individuals ≥60 years of age living in non–air-conditioned households in Montérégie, Quebec, during the 2017–2018 summer months. Methods: We gathered continuously measured indoor temperature and humidity from HOBO sensors and repeated health-related questionnaires about health-related symptoms administered across three periods of increasing outdoor temperatures, where the reference measurement (T1) occurred during a cool period with a target temperature of 18–22°C and two measurements (T2 and T3) occurred during warmer periods with target temperatures of 28–30°C and 30–33°C, respectively. We used generalized estimating equations with Poisson regression models and estimated risk ratios (RRs) between temperature, humidity, and each heat-related symptom. Results: Participants (n=277) had an average age (mean±standard deviation) of 72.8±7.02y. Higher indoor temperatures were associated with increased risk of dry mouth (T3 RR=2.5; 95% CI: 1.8, 3.5), fatigue (RR=2.3; 95% CI: 1.8, 3.0), thirst (RR=3.4; 95% CI: 2.5, 4.5), less frequent urination (RR=3.7; 95% CI: 1.8, 7.3), and trouble sleeping (RR=2.2; 95% CI: 1.6, 3.2) compared with T1. We identified a nonlinear relationship with indoor temperatures across most symptoms of interest. Discussion: This study identified that increasing indoor temperatures were associated with various health symptoms. By considering the prevalence of these early stage outcomes and indoor temperature exposures, adaptation strategies may be improved to minimize the burden of heat among vulnerable communities. https://doi.org/10.1289/EHP10291
Effect of glycated haemoglobin A1c on the survival of patients with oral squamous cell carcinoma and diabetes: a multicentre, retrospective, database cohort study
Authors: Chun-Yuan Chao, Sheng-Dean Luo, Wei-Chih Chen, Shao-Chun Wu, Tai-Jan Chiu, Yu-Ming Wang, Yao-Hsu Yang, Fu-Min Fang, Chung-Yi Li, Ching-Nung Wu
Journal: The Lancet Oncology (2022)
Radiotherapy and cancer status in Latin America: economic analysis of investment opportunities up to 2030
Authors: Gustavo R Sarria, David A Martinez, Ruben Del Castillo, Apolo Salgado, Luis Pinillos, Armando Felix, Ivan Bobadilla, Gustavo Ferraris, Alfredo Polo, Gustavo J Sarria
Journal: The Lancet Oncology (2022)
Carvedilol Achieves Higher Hemodynamic Response and Lower Rebleeding Rates Than Propranolol in Secondary Prophylaxis
Authors: Mathias Jachs, Lukas Hartl, Benedikt Simbrunner, David Bauer, Rafael Paternostro, Lorenz Balcar, Benedikt Hofer, Nikolaus Pfisterer, Michael Schwarz, Bernhard Scheiner, Albert F. Stättermayer, Matthias Pinter, Michael Trauner, Mattias Mandorfer, Thomas Reiberger
Journal: Clinical Gastroenterology and Hepatology (2022)

Carvedilol induces stronger decreases in hepatic venous pressure gradient (HVPG) than conventional nonselective β-blockers (ie, propranolol). Limited data exist on the efficacy of carvedilol in secondary prophylaxis of variceal bleeding.Patients undergoing paired HVPG measurements for guiding secondary prophylaxis with either carvedilol or propranolol were included in this retrospective analysis. All patients also underwent band ligation. Changes in HVPG and systemic hemodynamics were compared between the 2 groups. Long-term follow-up data on rebleeding, acute kidney injury, nonbleeding decompensation, and liver-related death were analyzed applying competing risk regression.Eighty-seven patients (carvedilol/propranolol, n = 45/42) were included in our study. The median baseline HVPG was 21 mm Hg (interquartile range, 18-24 mm Hg), and 39.1%/48.3%/12.6% had Child-Turcotte-Pugh A/B/C cirrhosis, respectively. Upon nonselective β-blocker initiation, HVPG decreased more strongly in carvedilol users (median relative decrease, -20% [interquartile range: -29% to -10%] vs -11% [-22% to -5%] for propranolol; P = .027), who also achieved chronic HVPG response more often (53.3% vs 28.6%; P = .034). Cumulative incidences for rebleeding (Gray test, P = .027) and liver-related death (P = .036) were significantly lower in patients taking carvedilol compared with propranolol. Notably, ascites development/worsening also was observed less commonly in carvedilol patients (P = .012). Meanwhile, acute kidney injury rates did not differ between the 2 groups (P = .255). Stratifying patients by HVPG response status yielded similar results. The prognostic value of carvedilol intake was confirmed in competing risk regression models.Carvedilol induces more marked reductions in HVPG than propranolol in secondary prophylaxis of variceal bleeding, and thus is associated with lower rates of rebleeding, liver-related death, and further nonbleeding decompensation.
Toripalimab (anti-PD-1) versus high-dose interferon-α2b as adjuvant therapy in resected mucosal melanoma: a phase II randomized trial
Authors: B. Lian, L. Si, Z.H. Chi, X.N. Sheng, Y. Kong, X. Wang, H. Tian, K. Li, L.L. Mao, X. Bai, B.X. Tang, X.Q. Yan, S.M. Li, L. Zhou, J. Dai, X.W. Tang, F.W. Ran, S. Yao, J. Guo, C.L. Cui
Journal: Annals of Oncology (2022)
Dual-responsive nanovaccine for cytosolic delivery of antigens to boost cellular immune responses and cancer immunotherapy
Authors: Yang Sui, Ji Li, Jiqiang Qu, Ting Fang, Hongyan Zhang, Jian Zhang, Zheran Wang, Mingyu Xia, Yinghui Dai, Dongkai Wang
Journal: Asian Journal of Pharmaceutical Sciences (2022)

Cancer vaccine contributing to the success of the treatment and prevention of tumors has attracted a huge attention as a strategy for tumor immunotherapy in recent years. A major challenge of cancer vaccine is to target cytosols of dendritic cells (DCs) in the lymph nodes (LNs) to enhance efficiency of antigen cross-presentation, which elicits high levels of cytotoxic T-lymphocytes to destruct tumor cells. Here, we address this issue by conjugating ovalbumin (OVA) to PEG-PCL using disulfide bond (-ss-), and the degradable pH-responsive polymer-PEI-PCL as delivery carrier. In addition, the mol ratio of PEG-PCL to PEI-PCL in the mixed micelles was tailored to deliver the OVA to LNs. Subsequently, CpG ODN1826, a TLR-9 agonist, was further introduced into a mixed micelle of 30 nm or less as a unique tumor vaccine. Importantly, the results demonstrated the mixed micelles with 1:1 mol of PCL-PEG and PCL-PEI can effectively migrate to distal LNs where antigen were efficiently captured by DCs, meanwhile, OVA was modified to the surface of mixed micelles via disulfide bonds (-ss-) for promotion efficiency of antigen cross-presentation. More surprisingly, combination of tumor vaccine with anti-PD-1, the therapy of ectopic melanoma (B16-OVA) and lung metastasis melanoma (B16-OVA) is excellent therapeutic effect. Taken together, our works offers a novel strategy for the cytosol delivery of antigens to achieve potent cancer immunotherapy.
Impact of health insurance type on access to vaccination and mortality due to COVID-19 on patients with cancer in Colombia: a cohort study
Authors: Aylen Vanessa Ospina-Serrano, Ricardo Bruges, Pedro Ramos, Laura Bernal, Sandra Aruachan, Alicia Quiroga, Giovanna Rivas, Isabel Munévar, William Mantilla, Guillermo Sánchez-Vanegas
Journal: The Lancet Oncology (2022)
Risk of Cancer in Children of Parents Occupationally Exposed to Hydrocarbon Solvents and Engine Exhaust Fumes: A Register-Based Nested Case–Control Study from Sweden (1960–2015)
Authors: Marios Rossides, Christina-Evmorfia Kampitsi, Mats Talbäck, Hanna Mogensen, Pernilla Wiebert, Maria Feychting, Giorgio Tettamanti
Journal: Environmental Health Perspectives (2022)

Background: It remains unclear whether parental occupational exposure to hydrocarbon solvents (HCS) or engine exhaust fumes (EEF) is associated with higher risks of cancer in the offspring. Objectives: Our aim was to estimate relative risks of childhood cancers associated with maternal or paternal exposure to aliphatic/alicyclic, aromatic, or chlorinated HCS or gasoline/diesel EEF. Methods: We conducted a case–control study in which individuals <20y old, born 1960–2014, were identified from the Swedish National Cancer Register (1960–2015) at first cancer diagnosis and matched to population controls (1 case:25 controls) on birth year and sex. Maternal and paternal occupation around the child's birth was retrieved for 9,653 cases and 172,194 controls and 12,521 cases and 274,434 controls, respectively, using information from six censuses and a nationwide register. Using the Swedish job-exposure matrix (SWEJEM), we assessed exposure to HCS and EEF (any or higher/lower). Odds ratios (ORs) and 95% confidence intervals (CIs) of 15 childhood cancer subtypes were estimated using conditional logistic regression models adjusted for several confounders. Results: Maternal exposure to aromatic HCS was associated with non-Hodgkin lymphoma (OR=1.64; 95% CI: 1.05, 2.58), aliphatic/alicyclic HCS with germ cell tumors (OR=1.52; 95% CI: 0.89, 2.59), and gasoline/diesel EEF with astrocytoma (OR=1.40; 95% CI: 1.04, 1.88), myeloid leukemia (OR=1.53; 95% CI: 0.84, 2.81), lymphomas (OR=1.60; 95% CI: 0.85, 3.02 for Hodgkin; OR=1.44; 95% CI: 0.71, 2.91 for non-Hodgkin), and epithelial tumors (OR=1.51; 95% CI: 0.93, 2.44). Paternal exposure to gasoline EEF was associated with Hodgkin lymphoma (OR=1.21; 95% CI: 1.01, 1.44) and soft tissue sarcomas (OR=1.22; 95% CI: 1.00, 1.48). No notable difference was observed between higher and lower exposure. Discussion: Our findings suggest that occupational exposure to HCS or EEF, especially in the mother, may increase the risk of some childhood cancers. They add to the growing literature on adverse effects from HCS and EEF in the child, but replication of these associations in other populations is warranted. https://doi.org/10.1289/EHP11035
New strategies for standardised and appropriate access to a complete acute lymphocytic leukaemia diagnostic panel for children in Mexico: an observational study
Authors: Daniela Arce-Cabrera, Pablo González-Montalvo, Hugo Antonio Romo-Rubio, Dinora Aguilar-Escobar, Nataly Mercado, Karla Guerrero-Gomez, Naomi Echeandia-Abud, Margarita González-Zamorano, Daniel Moreira, Paola Friedrich
Journal: The Lancet Oncology (2022)
Immune suppression in the tumor-draining lymph node corresponds with distant disease recurrence in patients with melanoma
Authors: Anneloes van Krimpen, Vivian I V Gerretsen, Evalyn E A P Mulder, Mandy van Gulijk, Thierry P P van den Bosch, Jan von der Thüsen, Dirk J Grünhagen, Cornelis Verhoef, Dana Mustafa, Joachim G Aerts, Ralph Stadhouders, Floris Dammeijer
Journal: Cancer Cell (2022)
Oral lichen planus and the Thr102Cys polymorphism of HTR2A: a pilot case-control study
Authors: Isabella Ferreira Michelon, Cainá Corrêa do Amaral, Tiago Fernandez Garcia, Geovanna Peter Corrêa, Adriana Beiersdorff Klug, Karine Duarte da Silva, Ana Carolina Uchoa Vasconcelos, Sandra Beatriz Chaves Tarquinio, Fernanda Nedel
Journal: The Lancet Oncology (2022)
Step-wise CAG@PLys@PDA-Cu2+ modification on micropatterned nanofibers for programmed endothelial healing
Authors: Bingcheng Yi, Boya Zhou, Zhenfeng Song, Lei Yu, Wenbo Wang, Wei Liu
Journal: Bioactive Materials (2022)

Native-like endothelium regeneration is a prerequisite for material-guided small-diameter vascular regeneration. In this study, a novel strategy is proposed to achieve phase-adjusted endothelial healing by step-wise modification of parallel-microgroove-patterned (i.e., micropatterned) nanofibers with polydopamine-copper ion (PDA-Cu2+) complexes, polylysine (PLys) molecules, and Cys-Ala-Gly (CAG) peptides (CAG@PLys@PDA-Cu2+). Using electrospun poly(l-lactide-co-caprolactone) random nanofibers as the demonstrating biomaterial, step-wise modification of CAG@PLys@PDA-Cu2+ significantly enhanced substrate wettability and protein adsorption, exhibited an excellent antithrombotic surface and outstanding phase-adjusted capacity of endothelium regeneration involving cell adhesion, endothelial monolayer formation, and the regenerated endothelium maturation. Upon in vivo implantation for segmental replacement of rabbit carotid arteries, CAG@PLys@PDA-Cu2+ modified grafts (2 mm inner diameter) with micropatterns on inner surface effectively accelerated native-like endothelium regeneration within 1 week, with less platelet aggregates and inflammatory response compared to those on non-modified grafts. Prolonged observations at 6- and 12-weeks post-implantation demonstrated a positive vascular remodeling with almost fully covered endothelium and mature smooth muscle layer in the modified vascular grafts, accompanied with well-organized extracellular matrix. By contrast, non-modified vascular grafts induced a disorganized tissue formation with a high risk of thrombogenesis. In summary, step-wise modification of CAG@PLys@PDA-Cu2+ on micropatterned nanofibers can significantly promote endothelial healing without inflicting thrombosis, thus confirming a novel strategy for developing functional vascular grafts or other blood-contacting materials/devices.
Current public perception of, and barriers to, palliative care in China: a mixed-methods study
Authors: Longtao He, Haojun Liao, Yangu Pan, Yixi Lu, Maodi Xu, Mandong Liu, Manting Chen, Shibei Ni, Yanling Geng, Chenyan Zhou, Fei Peng, Qihao Ran, Han Wu, Menghua Li, Nike Zhang, Jiamin Liu, Jianxia Lyu, Lei Zhang, Xiao Zang, Wei Chen, Minmin Luo, Ji Wu, Xue Chai, Qiongwen Zhang, Xiangshu Deng, Huamin Peng
Journal: The Lancet Oncology (2022)
Early detection of hepatocellular carcinoma with methylation and fragmentation signatures of circulating tumour DNA: a prospective, multicentre, case-control, observational study
Authors: Xinrong Yang, Jian Zhou, Jia Fan, De-Zhen Guo, Ao Huang, Chengcheng Ma, Minjie Xu, Wei Li, Zhixi Su
Journal: The Lancet Oncology (2022)
Low-dose irradiation for reversing immunotherapy resistance: how to translate?
Authors: Maria Ochoa-de-Olza, Jean Bourhis, George Coukos, Fernanda G Herrera
Journal: Journal for ImmunoTherapy of Cancer (2022)

The use of low-dose irradiation (LDI) for mobilizing innate and adaptive immunity is gaining interest among the scientific community. Recent evidence suggests that LDI can reprogramme the tumor microenvironment, induce inflammation and turn cold tumors susceptible to immunecheckpoint blockade therapy. Translating immuno-radiation preclinical findings in the clinic is more challenging than expected. We propose therapeutic strategies for combining LDI with immunotherapy, and emphasize the importance of pursuing clinical research to determine optimal radiation dosage, fractionation, volumes, and sequencing to stimulate immune-mediated tumor responses.
GCN2 inhibition sensitizes arginine-deprived hepatocellular carcinoma cells to senolytic treatment
Authors: Rindert Missiaen, Nicole M Anderson, Laura C Kim, Bailey Nance, Michelle Burrows, Nicolas Skuli, Madeleine Carens, Romain Riscal, An Steensels, Fuming Li, M Celeste Simon
Journal: Cell Metabolism (2022)
Endoscopy International Open – recently published
Journal: Endoscopy (2021)

Comment on: Overutilization of surgical resection for benign colorectal polyps: analysis from a tertiary care centerEndosc Int Open 2021; 09(05): E706-E712DOI: 10.1055/a-1380-3017 Comment on: Use of fully covered self-expanding metal biliary stents for managing endoscopic biliary sphincterotomy related bleedingEndosc Int Open 2021; 09(05): E667-E673DOI: 10.1055/a-1380-3268 Comment on: Colorectal endoscopic submucosal dissection using the pocket-creation method with single clip traction: a feasibility studyEndosc Int Open 2021; 09(05): E653-E658DOI: 10.1055/a-1372-3740
Endoscopy International Open – recently published
Journal: Endoscopy (2021)

Comment on: Impact of real-time use of artificial intelligence in improving adenoma detection during colonoscopy: A systematic review and meta-analysisEndosc Int Open 2021; 09(04): E513-E521DOI: 10.1055/a-1341-0457 Comment on: Endoscopic spectrum and practical classification of small bowel gastrointestinal stromal tumors (GISTs) detected during double-balloon enteroscopyEndosc Int Open 2021; 09(04): E507-E512DOI: 10.1055/a-1341-0404 Comment on: Feasibility study of a single-use balloon-assisted robotic colonoscope in healthy volunteersEndosc Int Open 2021; 09(04): E537-E542DOI: 10.1055/a-1352-3688
Endoscopy International Open – recently published
Journal: Endoscopy (2021)

Comment on: Gender disparities in advanced endoscopy fellowshipEndosc Int Open 2021; 09(03): E338-E342DOI: 10.1055/a-1311-0899 Comment on: Long-term clinical results of per-oral endoscopic myotomy (POEM) for achalasia: First report of more than 10-year patient experience as assessed with a questionnaire-based surveyEndosc Int Open 2021; 09(03): E409-E416DOI: 10.1055/a-1333-1883 Comment on: Outpatient ESD for challenging colorectal lesions: Is it feasible and safe for western countries?Endosc Int Open 2021; 09(03): E438-E442DOI: 10.1055/a-1333-1736
Highlights from Recent Cancer Literature
Journal: Cancer Research (2021)

A recent study has revealed the importance of Fat1 loss of function in the etiology of squamous cell carcinoma.Using genetic lossof-function studies in mouse models of skin squamous carcinoma, Pastushenko and colleagues demonstrated that deletion of the protocadherin Fat1 accelerated tumor initiation and progression.This was associated with acquisition of a hybrid epithelial-to-mesenchymal transition state and increased stemness.Through a series of transcriptomic and proteomic analyses and chromatin profiling, they identified a CAMK2-CD44-SRC signaling axis that controls adhesion remodeling driven by SOX2 and YAP1 transcriptional programs.Expert Commentary: Fat1 mutations are common in a number of tumor types and, together with the identification of potential drug vulnerabilities resulting from Fat1 loss, these findings may have wider implications for new targeted treatment options.(Image courtesy of Wikipedia Commons.)
Selected Articles from This Issue
Journal: Clinical Cancer Research (2021)

Activation of PI3K signaling has been identified previously as a mechanism of resistance to hormone therapy and HER2-targeting agents in breast cancer.Ballhausen and colleagues performed a dose-escalation phase I trial to assess the combination of the mTOR inhibitor everolimus, the aromatase inhibitor letrozole, and the HER2 antibody trastuzumab in patients with breast cancer and other solid tumors.This combination had an acceptable safety profile.At the recommended phase II dose, 5/32 patients (16%) showed a partial response to treatment, and these responses all occurred in women with breast cancer.Patients with HER2 amplification in cfDNA at baseline had shorter progression-free and overall survival compared to patients that lacked this alteration.These results support further clinical investigation of this combination, particularly in women with breast cancer.